Marie Michenkova, Sara Taki, Matthew C. Blosser, Hyea J. Hwang, Thomas Kowatz,
Fraser J. Moss, Rossana Occhipinti, Xue Qin, Soumyo Sen, Eric Shinn, Dengke
Wang, Brian S. Zeise, Pan Zhao, Noah Malmstadt, Ardeschir Vahedi-Faridi, Emad
Tajkhorshid, and Walter F. Boron.
Carbon dioxide transport across membranes.
Interface Focus, 11:20200090, 2021.
MICH2021-ET
Carbon dioxide (CO2) movement across cellular membranes is passive
and,
at a nanoscopic scale, governed by Fick’s law of diffusion. Until
recently, we
believed that gases cross biological membranes exclusively by
dissolving
in and then diffusing through membrane lipid. However, the observation
that some membranes are CO2 impermeable led to the discovery of a gas
molecule’s moving through a channel, namely, CO2 diffusion through
aquaporin-1 (AQP1).
Later work demonstrated CO2 diffusion through rhesus
(Rh) proteins and NH3 diffusion through both AQPs and Rh proteins. The
tetrameric
AQPs exhibit differential selectivity for CO2 versus NH3 versus H2O,
reflecting
physico-chemical differences among the small molecules, as well as
among the hydrophilic monomeric pores and hydrophobic central pores of
various AQPs. Preliminary work suggests that NH3 moves through the
mono-
meric pores of AQP1, whereas CO2 moves through both monomeric and
central pores. Initial work on AQP5 indicates that it is possible to
create a
metal-binding site on the central pore’s extracellular face, thereby
block CO2
movement. The trimeric Rh proteins have monomers with hydrophilic
pores
surrounding a hydrophobic central pore. Preliminary work on the
bacterial
Rh homologue AmtB suggests that gas can diffuse through the central
pore
and three sets of interfacial clefts between monomers. Finally,
initial work indi-
cates that CO2 diffuses through the electrogenic Na/HCO3 cotransporter
NBCe1. At least in some cells, CO2-permeable proteins could provide
impor-
tant pathways for transmembrane CO2 movements. Such pathways could be
amenable to cellular regulation and could become valuable drug
targets.
